Multi-disciplinary investigations were carried out in a Holocene eolian loess-soil profile in the centre of the Chinese Loess Plateau at the transition between the arid Mongolian steppe and the semi-arid mixed forest, and also the transitional zone between nomadism and the rain-fed cereal agriculture in history. The cultural remains of an earliest rain-fed cereal agriculture, and also the remains of a Bronze Age nomadic community identified in the profile indicate that the regional emergence and decline of the rain-fed cereal agriculture was closely connected with the change in dust accumulation and soil formation. The climatic proxies derived from the profile show that monsoonal climatic variation, especially precipitation behind the pedogenic change, was ultimately responsible for the cultural and land-use change over the Loess Plateau. Increased precipitation brought on by southeast monsoon, conditioned the domestication and cultivation of millets in the southern part of the region during 8000–7000 a BP at the beginning of the Holocene climatic optimum. Sufficient precipitation and the well-developed fertile soils facilitated the expansion of millets cultivation to the northern Loess Plateau and the southern Mongolian Plateau between 7000 a BP and 3600 a BP. Reduced precipitation and deteriorated land-use conditions because of intensified northwest monsoon at the end of the Holocene climatic optimum caused a regional desertion by the arable farming communities and the invasion of the nomads in the northern part of the Loess Plateau from ca. 3600 a BP during the Bronze Age. Monsoonal climatic change and the resultant pedogenic change dramatically affected the cultural development over the Loess Plateau during the Holocene.